Carnegie Mellon University

Marcel Bruchez

Marcel Bruchez

Professor, Chemistry
Professor, Biological Sciences
Director, Molecular Biosensor and Imaging Center

Education

1995–1998     Ph.D. Physical Chemistry, University of California, Berkeley

Research

Fluorescence, biological microscopy, imaging, light-harvesting structures, biosensors, single molecule biophysics, protein translation, protein folding, protein trafficking

Biological research has been propelled by the availability of fluorescent proteins that allow dynamic microscopy of living cells. The repertoire of intrinsically fluorescent proteins is substantially less diverse in form and function than the repertoire of chemically synthetized dye molecules, yet genetic targeting provides such a significant advantage that probes 2-10-fold less bright than typical organic dyes are routinely used in fluorescence imaging. Our work is focused on developing tools that couple the best of the synthetic dyes with the advantages of genetic targeting. These novel probes allow unique investigations of cell-biological and biochemical processes fundamental to our understanding of health and diseases.

Projects

New tools for single molecule investigations and superresolution imaging

The limits of microscopy can be expanded dramatically by design and use of the right fluorescent dye molecules. Research in this area is focused on enhancing the brightness, stability and activation properties of dye molecules useful with our genetically expressed protein targets. We exploit these probes with sensitive fluorescence imaging to detect biological processes at higher resolution and longer timescales than conventionally achieved in fluorescence microscopy. These tools are applied to study the translation and folding of single molecules by the protein synthesis machinery of eukaryotic cells (the ribosome).

Targeted tools for protein trafficking

The endocytic/exocytic processes are fundamental to a wide range of biological phenomena, including immunity, allergy and synaptic transmission. Utilizing engineered proteins that fold well in the secretory pathway of cells and bind to otherwise weakly fluorescent dye molecules, we have developed a series of fluorescent indicators that are “activated by targeting.” These ratiometric dyes enable direct interrogation of the endocytic trafficking process and the protein fate after stimulation by biological ligands or drugs. Trafficking of receptors under the influence of genetic mutations and pharmacologic treatments provides new mechanistic and therapeutic insights into receptor action in these important biological processes.

Publications

Affibody-Targeted Fluorogen Activating Protein for in vivo Tumor Imaging
Wang, Y., Ballou, B., Schmidt, B.F., Andreko, S., St.Croix, C.M., Watkins, S.C., Bruchez, M.P., Chemical Communications. 2017. DOI: 10.1039/c6cc09137g

Combining Novel Probes and High Resolution Imaging to Dissect Mitochondrial Function in Living Systems
Pena, K., Larsen, M., Calderon, M., Tsang, M., Watkins, S., Bruchez, M., & St. Croix, C. (2017). Microscopy and Microanalysis, 23(S1), 1170-1171. doi:10.1017/S1431927617006511

Fluoromodules Consisting of a Promiscuous RNA Aptamer and Red or Blue Fluorogenic Cyanine Dyes: Selection, Characterization, and Bioimaging
Xiaohong Tan, Tudor P. Constantin, Kelly L. Sloane, Alan S. Waggoner, Marcel P. Bruchez, and Bruce A. Armitage, Journal of the American Chemical Society 2017 139 (26), 9001-9009, DOI: 10.1021/jacs.7b04211

Genetically Targeted Ratiometric and Activated pH Indicator Complexes (TRApHIC) for Receptor Trafficking
Lydia A. Perkins, Qi Yan, Brigitte F. Schmidt, Dmytro Kolodieznyi, Saumya Saurabh, Mads Breum Larsen, Simon C. Watkins, Laura Kremer, and Marcel P. Bruchez, Biochemistry, DOI: 10.1021/acs.biochem.7b01135

Tagging of Endogenous BK Channels with a Fluorogen-Activating Peptide Reveals β4-Mediated Control of Channel Clustering in Cerebellum
Pratt CP, Kuljis DA, Homanics GE, et al. Frontiers in Cellular Neuroscience. 2017;11:337. doi:10.3389/fncel.2017.00337.

Multiexcitation Fluorogenic Labeling of Surface, Intracellular, and Total Protein Pools in Living Cells
Naganbabu, M, Perkins, LA, Wang, Y, Kurish, J, Schmidt, BF, Bruchez, MP, Bioconjug. Chem. 2016; 27 (6):1525-31. PubMed PMID:27159569.

RNA G-Quadruplex Invasion and Translation Inhibition by Antisense γ-Peptide Nucleic Acid Oligomers
Oyaghire, SN, Cherubim, CJ, Telmer, CA, Martinez, JA, Bruchez, MP, Armitage, BA, Biochemistry. 2016; 55 (13):1977-88. PubMed PMID:26959335.

A genetically targetable near-infrared photosensitizer
He, J, Wang, Y, Missinato, MA, Onuoha, E, Perkins, LA, Watkins, SC, St Croix, CM, Tsang, M, Bruchez, MP, Nat. Methods. 2016; 13 (3):263-8. PubMed PMID:26808669.

A Fluorogenic Green-Inside Red-Outside (GIRO) Labeling Approach Reveals Adenylyl Cyclase-Dependent Control of BKα Surface Expression
Pratt, C.P., He, J., Wang, Y., Barth, A.L., Bruchez, M.P., Bioconjugate Chemistry. 2015; 26(9):1963-71. doi: 10.1021/acs.bioconjchem.5b00409.

Kinetically tunable photostability of fluorogen activating protein-fluorogen complexes
Saurabh, S., Zhang, M., Mann, V.R., Costello, A.M., Bruchez, M.P., ChemPhysChem. 2015; 16(14):2974-80. doi: 10.1002/cphc.201500587.

In Vitro Reversible Translation Control Using γ-PNA Probes
Canady, T.D., Telmer, C.A., Oyaghire, S.N., Armitage, B.A., Bruchez, M.P., Journal of the American Chemical Society. 2015;137(32):10268-75. doi: 10.1021/jacs.5b05351.

Genetically targeted fluorogenic macromolecules for subcellular imaging and cellular perturbation
Magenau A.J., Saurabh S, Andreko S.K., Telmer C.A., Schmidt B.F., Waggoner A.S., Bruchez M.P., Biomaterials. 2015;66:1-8. Doi: 10.1016/j.biomaterials.2015.07.002.

Dark dyes-bright complexes: fluorogenic protein labeling
Bruchez M.P., Current Opinion in Chemical Biology. 2015; 27: 18-23. Doi 10.1016/j.cbpa.2015.05.014

Advances in chemical labeling of proteins in living cells
Yan Q., Bruchez M.P., Cell and Tissue Research. 2015;360(1):179-194. Doi 10.1007/s00441-105-2145-4.

Appointments

YearsPosition
2017–present Professor of Chemistry and Biological Sciences, Carnegie Mellon University
2014–present Director, Molecular Biosensor and Imaging Center, Carnegie Mellon University
2011–2017 Associate Professor of Chemistry and Biological Sciences, Carnegie Mellon University
2011–2014 Associate Director, Molecular Biosensor and Imaging Center, Carnegie Mellon University
2006–2011 Associate Research Professor of Chemistry, Carnegie Mellon University
1998–2006 Founder, Principal Scientist Quantum Dot Corporation
1995–1998 Ph.D. Physical Chemistry, University of California, Berkeley
1991–1995 B.S. Chemistry, Massachusetts Institute of Technology

Awards and Distinctions

YearsAward
2006 Rank Prize Optoelectronics Award
2004 Honoree “Top 100 Young Innovators” Technology Review Magazine
2004 R&D 100 Award for Innovative Products based on Qdot Conjugate technology
2003 Science Magazine Top Ten Scientific Innovations of 2003 — “Quantum dots for biological detection”
1995 National Science Foundation Graduate Research Fellowship